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Biomedical subjects

G Rouleau

Publications and source records attributed to G Rouleau.

At least 37 records · Page 2Linked to original sources
PubMed1995

Superoxide dismutase activity in lymphoblastoid cells from motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients.

Point mutations in the gene encoding Cu,Zn superoxide dismutase (SOD1) are associated with autosomal dominant familial amyotrophic lateral sclerosis (FALS). We have measured Cu,Zn SOD activity in lymphoblastoid cells from affected and at risk FALS patients carrying mutations in the SOD1 gene, FALS patients without mutations in the SOD1 gene, individuals affected by the sporadic form of the disease (SALS), normal controls and individuals with other neurological abnormalities. The results show a significant decrease in Cu,Zn SOD activity in affected and at risk FALS individuals as compared to FALS patients without mutations, SALS individuals, normal and neurological controls. It is concluded that decreased SOD activity may contribute, together with other as yet unknown factors, to motor neurone demise.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Newborn apnea caused by a neurofibroma at the craniocervical junction.

The authors report, for the first time, the finding by magnetic resonance imaging of a neurofibroma at the craniocervical junction with upper cervical cord and lower brainstem compression causing complete apnea from birth. Subsequent subtotal resection of the neurofibroma resulted in the successful extubation of a previously ventilator-dependent patient. After a two month period of breathing spontaneously, the newborn developed an upper respiratory tract infection and was reintubated. The patient, unable to be weaned off of the respirator, was extubated and expired shortly thereafter, at the age of five months. The authors suggest that in newborns with unexplained apnea, MRI of the cranio-cervical junction is indicated. Certain patients may be discovered who have less compromised cervico-medullary function and are afflicted by less aggressive forms of neurofibromatosis type 1. These patients may benefit permanently from a surgical decompression.

Apnea↗
PubMed1994

Sweat gland vacuoles in Unverricht-Lundborg disease: a clue to diagnosis?

There has been no reported pathologic abnormality outside the central nervous system in patients with Unverricht-Lundborg disease (ULD). We report membrane-bound vacuoles with clear contents in eccrine clear cells and dark cells in five of seven patients with ULD, as well as in one clinically unaffected sibling. Vacuoles were not seen in the biopsies of two patients and of eight controls with Lafora's disease. These findings, though not entirely specific, suggest that skin biopsy may serve as a diagnostic aid to give supportive evidence for ULD.

Adolescent↗
PubMed1994

Molecular cytogenetic analysis of a series of 23 DiGeorge syndrome patients by fluorescence in situ hybridization.

The authors have studied a series of 23 DiGeorge syndrome patients by prometaphase chromosome analysis and/or by FISH with a set of 6 cosmid probes spanning the previously described commonly deleted region. Four patients display a cytogenetically visible interstitial deletion in band 22q11.2, whereas the other 18 patients exhibit a molecular deletion evidenced only by FISH analysis. For 21 of the patients studied, the deletion encompasses the 6 loci tested, while for one, only the most telomeric of these loci is conserved. The last patient does not show any deletion with the probes used.

Adolescent↗
PubMed1993

A set of STS assays targeting the chromosome 22 physical framework markers.

The widespread use of the sequence-tagged site (STS) as a quick, efficient, and reproducible assay for comparing physical and genetic map information promises to facilitate greatly long-range goals of the mapping of the human genome. We have designed 21 STS assays for loci on human chromosome 22. These assays primarily tag the physical framework markers of the long arm of 22, but additional assays have been designed from known genes and loci in the neurofibromatosis 2 (NF2) region. The availability of these assays will make these loci available to the research community without physical transfer of materials and will serve as start points for further efforts to physically map chromosome 22 with yeast artificial chromosome clones.

Animals↗
PubMed1993

Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy.

Expansion of the long (CAG; glutamine)n repeat in the first exon of the X-linked human androgen receptor gene (hAR) causes spinal and bulbar muscular atrophy, frequently in association with mild androgen insensitivity. The relevant normal motor neurons are preferentially stimulated by androgen, however no motor neuron disorder occurs with any other known AR mutation, including those that cause complete androgen insensitivity. We have found that a polyglutamine (Gln) expanded AR transactivates an androgen-responsive reporter gene subnormally. Other groups have reported that a poly Gln-deleted AR transactivates normally. A parsimonious interpretation of all these facts is that poly Gln expansion causes the AR to lose a function that is necessary for full androgen sensitivity and to gain a function that is selectively motor neuronotoxic.

Androgens↗
PubMed1992

Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.

Ewing's sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11;22) (q24;q12) chromosome translocation, the breakpoints of which have recently been cloned. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1.

Amino Acid Sequence↗
PubMed1992

Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints.

Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12). The cos5 locus, previously identified in the vicinity of the chromosome 22 breakpoint of this translocation, was shown by in situ hybridization on interphase nuclei to lie between VIIIF2 and LIF, two loci located on either side of the breakpoint and at a distance of less than 2,000 kb. The progressive expansion of this locus by chromosome walking led to the construction of a 300 kb contig, which finally crossed the breakpoint. The subsequent cloning of the two translocation junction fragments of a PN, followed by the molecular characterization of the translocation breakpoints of 20 ES and PN, showed that most chromosome 22 breakpoints are clustered within a small, 2 kb region. In contrast, the chromosome 11 breakpoints are scattered over a region of at least 40 kb. The translocation leads to the synthesis of chimeric transcript that links sequences from chromosomes 22 and 11. Finally, no evidence was found of any specific difference in the position of ES and PN translocation breakpoints.

Bone Neoplasms↗
PubMed1992

Rapid isolation of cosmids from defined subregions by differential Alu-PCR hybridization on chromosome 22-specific library.

A method based on the differential screening of a chromosome-specific cosmid library with amplified inter-Alu sequences obtained from a set of somatic cell hybrids has been developed to target the isolation of probes from predefined subchromosomal regions. As a model system, we have used a chromosome 22-specific cosmid library and four cell hybrids containing different parts of this chromosome. The procedure has identified cosmids that demonstrate differential hybridization signals with Alu-PCR products from these cell hybrids. We show, by in situ hybridization or individual mapping, that their hybridization pattern is indicative of their sublocalization on chromosome 22, thus resulting in a large enrichment factor for the isolation of probes from specific small chromosome subregions. Depending on the local Alu-sequence density, from 3 to 10 independent loci per megabase of genome can thus be identified.

Animals↗
PubMed1991

Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity.

BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. METHODS AND RESULTS: We evaluated 23 families with familial amyotrophic lateral sclerosis for linkage of the gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score--5.03--was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P less than 0.0001) of genetic-locus heterogeneity in the families. CONCLUSIONS: The localization of a gene causing familial amyotrophic lateral sclerosis provides a means of isolating this gene and studying its function. Insight gained from understanding the function of this gene may be applicable to the design of rational therapy for both the familial and sporadic forms of the disease.

Adolescent↗
PubMed1991

Mapping of human chromosome 22 with a panel of somatic cell hybrids.

The adenylosuccinate lyase (ADSL) which is essential for generating adenylate, maps to the long arm of chromosome 22. By using a Chinese hamster ovary cell line deficient in ADSL activity, we have constructed a set of 17 somatic cell hybrids containing defined regions of human chromosome 22. This panel was extended with six additional hybrids, obtained in other laboratories using various methods of selection. Southern analysis of the hybrids with 38 chromosome 22 probes defined 14 different subregions which could be linearly organized on the long arm of chromosome 22. The order of the probes thus deduced is fully compatible with their previous localization and with the genetic map. The ADSL gene was further sublocalized between the MB and D22S22. This panel, which enables the rapid assignment of chromosome 22 single copy probes to small subregions, will be an important tool in the construction of a detailed physical map of this part of the genome.

Adenylosuccinate Lyase↗
PubMed1990

Assessment of chromosome 22 anomalies in neurinomas by combined karyotype and RFLP analyses.

We report the cytogenetic study of 28 neurinomas; sixteen of them were also analysed using 11 polymorphic DNA markers for the loss of alleles of chromosome 22. Partial or total loss of chromosome 22 was found in nine cases. The results of the two approaches appear homogeneous, however, three tumors that yielded only cells with normal karyotypes demonstrated loss of constitutional heterozygosities. One of the tumors, which displayed an isodicentric or isopseudodicentric 22, was obtained in a patient with von Recklinghausen neurofibromatosis. It appears that loss of chromosome 22 is a characteristic of neurinomas whatever their context of occurrence.

Alleles↗
PubMed1990

Localization of 27 DNA markers to the region of human chromosome 22q11-pter deleted in patients with the DiGeorge syndrome and duplicated in the der22 syndrome.

DiGeorge syndrome is a human developmental field defect with the pathological features of an abnormality of embryogenesis at 4 to 6 weeks of gestation. Cytogenetic analyses of patients have revealed a number of instances of monosomy 22q11-pter in this condition. We have analyzed 52 DNA markers that map to 22q11-pter and have found 27 that are deleted in DiGeorge syndrome patients with known monosomy for part of this region and that are duplicated in patients with the der22 syndrome. The set of clones mapping to the DiGeorge region was further assigned to a proximal or a distal location within the deletion.

Base Sequence↗
PubMed1990

Mapping of human chromosome 22 by in situ hybridization.

The second smallest chromosome of the human karyotype, i.e., chromosome 22, is involved in many congenital or acquired structural aberrations. This variety can be taken advantage of to determine the exact linear order, from centromere to telomere, of cloned probes and chromosomal breakpoints. Eleven probes were localized with respect to breakpoints of 11 der(22) of independent cell lines using in situ hybridization on metaphasic spreads. The deduced order of the tested probes and that of the breakpoints are in complete agreement with the published genetic map and the karyotypic analysis, respectively. This approach enables a correlation of the genetic map with the chromosomal banding.

Cell Line↗
PubMed1990

The neuroepithelioma breakpoint on chromosome 22 is proximal to the meningioma locus.

The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids. These two probes have further been shown to be genetically linked at theta = 0.0 and a lod score of 5.3. The two probes were unaffected by a partial deletion of the chromosome 22 long arm of a meningioma, showing that the meningioma locus is distal to that of the neuroepithelioma.

Blotting, Southern↗
PubMed1987

Common pathogenetic mechanism for three tumor types in bilateral acoustic neurofibromatosis.

Bilateral acoustic neurofibromatosis (BANF) is a genetic defect associated with multiple tumors of neural crest origin. Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients. This indicates a common pathogenetic mechanism for all three tumor types. The two neurofibromas were among three taken from the same patient, and both showed loss of identical alleles demonstrating that the same chromosome suffered deletion in both tumors. The third neurofibroma from this patient showed no detectable loss of heterozygosity, which suggests the possibility of a more subtle mutational event that affects chromosome 22. In the two acoustic neuromas, only a portion of chromosome 22 was deleted, narrowing the possible chromosomal location of the gene that causes BANF to the region distal to the D22S9 locus in band 22q11. The identification of progressively smaller deletions on chromosome 22 in these tumor types may well provide a means to clone and characterize the defect.

Alleles↗
PubMed1987

Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers.

The combined effects of dexamethasone treatment (1 mg/Kg/day) plus denervation (DEX-DEN), were studied at 7, 13, and 28 days by microscopic, biochemical, and physiological techniques in plantaris and soleus muscles of adult rats. The results were compared with corresponding dexamethasone-treated (DEX) and denervated (DEN) muscles and appropriate controls. There was a significantly more marked atrophy of all fiber types in the DEX-DEN plantares at 7 and 13 days than in either DEX or DEN muscles. The degree of atrophy was greatest in type 2B fibers in DEX-DEN plantares. Electron microscopy revealed a severe preferential depletion of thick myofilaments in DEX-DEN plantares and solei but not in DEX or DEN muscles. The thick myofilament depletion in DEX-DEN muscles occurred in addition to a severe overall reduction of myofibrillar caliber. Gel electrophoresis showed a marked preferential decrease of myosin heavy chain in DEX-DEN plantares and solei, but not in either DEX or DEN muscles. Myosin light chains were also markedly reduced in DEX-DEN plantares and solei. In vitro physiological studies showed a marked reduction of the denervation-induced twitch potentiation in DEX-DEN solei. Maximal tetanic tension (20 Hz stimulation) per gram weight of muscle as well as the twitch-tetanus ratio was significantly reduced only in DEX-DEN solei in relation to controls. Myosin depletion in DEX-DEN muscles may be due to a severe preferential inhibition of its synthesis coupled with an accelerated catabolism.

Actins↗